23 research outputs found
Efficacy and safety of abatacept in active primary Sjogren's syndrome:results of a phase III, randomised, placebo-controlled trial
Objectives To evaluate efficacy and safety of abatacept in adults with active primary Sjogren's syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial. Methods Eligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjogren's Syndrome Disease Activity Index [ESSDAI] >= 5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored. Results Of 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI - 3.2 abatacept vs -3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified. Conclusions Abatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity
Evaluation of tear osmolarity in non-Sjögren and Sjögren syndrome dry eye patients with the tearlab system
Differences in Human Meibum Lipid Composition with Meibomian Gland Dysfunction Using NMR and Principal Component Analysis
Changes in the composition of meibum lipids in meibomian gland dysfunction were measured by proton nuclear magnetic resonance spectroscopy
Analysis of the Composition of Lipid in Human Meibum from Normal Infants, Children, Adolescents, Adults, and Adults with Meibomian Gland Dysfunction Using 1H-NMR Spectroscopy
The changes in cholesteryl ester measured using 1H-NMR spectroscopy could be used as a molecular marker for meibomian gland dysfunction (MGD) and could potentially be applied to follow the efficacy of drug therapy of MGD
Physical Changes in Human Meibum with Age as Measured by Infrared Spectroscopy
Both lipids and mucins contribute to the stability of the tear film and lipids may
inhibit tears from evaporating. Younger people have lower lipid viscosity, higher lipid
volume, and a lower rate of tear evaporation. Since age-related changes in human meibum
composition and conformation have never been investigated, as a basis for the study of
lipid-associated changes with meibomian gland dysfunction, we used the power of infrared
spectroscopy to characterize hydrocarbon chain conformation and packing in meibum from
humans without dry eye symptoms in relation to age and sex. Meibum from normal human
donors ranging in age from 3 to 88 years was studied. Meibum phase transitions were
quantified by fitting them to a 4-parameter 2-state sigmoidal equation. Human meibum order
and phase transition temperatures decrease with age and this trend may be attributed to
lipid compositional changes. If meibum has the same thermodynamic properties on the
surface of the tears as it does on the lid margin, a decrease in lipid-lipid interaction
strength with increasing age could decrease the stability of tears since lipid-lipid
interactions on the tear surface must be broken for the tear film to break up. This study
also serves as a foundation to examine meibum conformational differences in meibum from
people with meibomian gland dysfunction
Glycoprotein 340 in Normal Human Ocular Surface Tissues and Tear Film
The tear film is a complex mixture of secreted fluid, ions, proteins, glycoproteins, and lipids that lubricates and protects the ocular surface. Recently, several antimicrobial peptides have been described in the tear fluid. In this study, we describe the presence of the large secreted glycoprotein gp340 in the tear film. Western blot analysis showed that gp340 is abundant in secreted tears and in the lacrimal glands. Lesser amounts of gp340 were detected in the cornea and conjunctiva. Consistent with Western blot data, reverse transcription-PCR and real-time quantitative PCR showed that gp340 transcripts were abundant in lacrimal gland tissue and were also present in the cornea and conjunctiva. Immunohistochemistry localized gp340 to the acinar cells of the lacrimal gland and the deeper layers of the conjunctival epithelium. gp340 was not detected in conjunctival goblet cells. In the cornea, gp340 was present only in a peripheral band of basal epithelial cells, suggesting that gp340 may play a role in the cycle of corneal epithelial renewal. To determine if tear film gp340 may function as a bacterial agglutinin as it does in saliva, tears were incubated with streptococcal cells and the formation of bacterial aggregates was monitored. Addition of tears to late-exponential-phase Streptococcus mutans cells resulted in time- and dose-dependent aggregation of the bacteria. Furthermore, Western blot analysis confirmed the presence of cell-associated gp340 in isolated bacterial aggregates. The ocular pathogen Staphylococcus aureus, but not Pseudomonas aeruginosa, also aggregated when incubated with tears. These results suggest that gp340 is a normal component of the tear film and that the glycoprotein may function as a bacterial agglutinin
Human Meibum Lipid Conformation and Thermodynamic Changes with Meibomian-Gland Dysfunction
Principle component analyses of infrared spectra of human meibum indicate that human meibum collected from normal donors is less ordered than meibum from donors with meibomian gland dysfunction. Model studies indicate that changes in the amount of lipid saturation, rather than the amount of cholesterol esters, could be a factor in the observed conformational differences